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首页> 外文期刊>Cell Division >Gauchos and ochos: a Wee1-Cdk tango regulating mitotic entry
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Gauchos and ochos: a Wee1-Cdk tango regulating mitotic entry

机译：高乔和牛：调节有丝分裂进入的Wee1-Cdk探戈

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The kinase Wee1 has been recognized for a quarter century as a key inhibitor of Cyclin dependent kinase 1 (Cdk1) and mitotic entry in eukaryotes. Nonetheless, Wee1 regulation is not well understood and its large amino-terminal regulatory domain (NRD) has remained largely uncharted. Evidence has accumulated that cyclin B/Cdk1 complexes reciprocally inhibit Wee1 activity through NRD phosphorylation. Recent studies have identified the first functional NRD elements and suggested that vertebrate cyclin A/Cdk2 complexes also phosphorylate the NRD. A short NRD peptide, termed the Wee box, augments the activity of the Wee1 kinase domain. Cdk1/2-mediated phosphorylation of the Wee box (on T239) antagonizes kinase activity. A nearby region harbors a conserved RxL motif (RxL1) that promotes cyclin A/Cdk2 binding and T239 phosphorylation. Mutation of either T239 or RxL1 bolsters the ability of Wee1 to block mitotic entry, consistent with negative regulation of Wee1 through these sites. The region in human somatic Wee1 that encompasses RxL1 also binds Crm1, directing Wee1 export from the nucleus. These studies have illuminated important aspects of Wee1 regulation and defined a specific molecular pathway through which cyclin A/Cdk2 complexes foster mitotic entry. The complexity, speed, and importance of regulation of mitotic entry suggest that there is more to be learned.
机译：四分之一世纪以来，Wee1激酶被认为是细胞周期蛋白依赖性激酶1（Cdk1）和真核生物中有丝分裂进入的关键抑制剂。尽管如此，对Wee1的调控尚不十分清楚，其大的氨基末端调控域（NRD）仍未阐明。已有证据表明，细胞周期蛋白B / Cdk1复合物通过NRD磷酸化相互抑制Wee1活性。最近的研究已经确定了第一个功能性NRD元素，并建议脊椎动物细胞周期蛋白A / Cdk2复合物也可以使NRD磷酸化。一种短的NRD肽，称为Wee框，可增强Wee1激酶结构域的活性。 Cdk1 / 2介导的Wee框（在T239上）的磷酸化可拮抗激酶活性。附近区域带有一个保守的RxL基序（RxL1），该基序可促进细胞周期蛋白A / Cdk2结合和T239磷酸化。 T239或RxL1的突变增强了Wee1阻止有丝分裂进入的能力，这与Wee1通过这些位点的负调控相一致。人体Wee1中​​包含RxL1的区域也与Crm1结合，指导Wee1从细胞核中输出。这些研究阐明了Wee1调控的重要方面，并定义了细胞周期蛋白A / Cdk2复合物促进有丝分裂进入的特定分子途径。有丝分裂进入的调节的复杂性，速度和重要性表明，还有很多事情需要学习。

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